Your Digest for Tuesday, Sep 19, 2023 09:59 PM


[!INFO] The strongest index of CVD risk is "non HDL cholesterol".
This is reported by the lab as the Total cholesterol - HDL cholesterol

Lipid transport in the blood


mitochondrialInheritanceCartoon.png
#2021BSQ-JUL Q34
So mitochondrial disorders could be caused by defects in mitochondrial DNA or defects in nuclear DNA. (but these "mitochondrial diseases" don't show "mitochondrial inheritance")

"the CEO of Pearson kissed Leia while MELAS, MERRF and NARP Looked-ON"

Leber hereditary optic neuropathy

[!TIP] Mnemonic: Affects, eyes, ears, brain, heart and movement -everything you need for sports ;)
MELASmnemonic.png


#2021BSQ-JUL Q25

[!INFO] The ciliary ganglion an it's associated nerves are important in understanding the autonomic innervation of the eye :
ciliaryGanglionAnatomy.png
Short ciliary nerves contains sympathetic and parasympathetic nerves.
Long ciliary nerves only contain sympathetic (but also sensory) fibers.

  1. Muller's muscle (Superior tarsal muscle) - contributes to 1 - 2 mm of eye lid retration; innervated by the sympathetic system.

Source

Immune system

Components of the innate immune system:

Macrophage function

Macrophages function as

  1. Mediators of inflammation (see diagram below)
  2. Effectors of the immune response

Inflammatory role:
inflammatoryRoleMacrophages.png

In addition to phagocytic and microbicidal actions, macrophages secrete cytokines which stimulate repair and sustain inflammation.

Effector role:
Macrophages function as effectors of adaptive immunity

Natural killer cells

naturalKillerCells.png
NK cells are lymphocytes but do no express antigen specific receptors like T or B cells.
Balance between inhibitory and activating stimulation decides whether the NK cell kills the target cell or not.

NK cells can destroy cells without previous sensitization.

Killing is mediated by cytotoxic molecules which are stored within secretory lysosomes, a specialized exocytic organelle found in NK cells - Source

Important in destroying tumour cells.
Tumour cells may downregulated MHC-class I molecules to avoid detection by T cells. But loss of MHC-class I will activate NK cells. Therefore, NK cells and T cells function in a complementary fashion to eliminate tumour cells.

Antigen presenting cells

The main type of antigen presenting cell is the dendritic cell.
Other cells are also involved.
Dentric cell type 1: Dentritic cells

Macrophages and B cells can also act as antigen presenting cells.

Ataxia telangiectasia

#autosomal-Recessive
ataxiaTelangiectasia.png
There is a mutation in the ATM gene.

[!INFO] This gene is necessary for the action of tumour suppressors p53 and BRCA1.

One manifestation of the disease is increased susceptibility to malignancies.


Tumour markers

#2021BSQ-JUL Q31

  1. Alpha-fetoprotein (AFP) - Liver cancer, germ cell tumors, particularly testicular cancer
  2. Neuron-Specific Enolase (NSE) - Neuroendocrine tumors, small cell lung cancer
  3. Epidermal Growth Factor Receptor (EGFR) - Non-small cell lung cancer, colorectal cancer

\Large{RR=\frac{risk\ of\ event\ in\ one\ group}{risk\ of\ event\ in\ other\ group}}
If the exposure lowers the risk of an outcome, then the relative risk will be less than 1. Source

\Large{OR=\frac{odds\ of\ event\ in\ one\ group}{odds\ of\ event\ in\ other\ group}}
In retrospective studies (case-control) studies, the total number of people "at risk" is not available. RR cannot be calculated. OR must be used.
Source

To determine "Whether the observed effect of an intervention is clinically important",
we use
$$
\Large{ARR = Risk\ in\ Control\ group - Risk\ in\ intervention\ group}
$$

In the above example, the baseline risk of death was 44% and ligation, with an ARR of 16% reduced this risk to 28%, which is nearly two-third (=0.28/0.44 = 0.636 or 64%) of the baseline risk. This is a medium-sized “relative” effect. However, if the baseline risk of death had been 20%, then a 16% ARR would bring the risk down to 4%, i.e. to about one-fifth of the original risk, a much bigger change in relative terms
\Large{RRR = \frac{ARR}{risk\ in\ \mathbf{control}\ group}}

Attributable risk

attributableRisk.png

$$
\Large{Attributble\ Risk = Risk\ in\ Exposed - Risk\ in\ Unexposed}
$$

Source

Hypothesis testing

Types of tests

ANOVA

[!INFO] The basic principle of ANOVA
basisOfANOVA.png
Which variance (between the groups of within the groups) accounts for most of the variation seen in the population?

Tests the hypothesis that the means of two or more populations are equal.
There are different types of ANOVA:

One way ANOVA is an extension of the t-test for independent samples to more than two groups. (i.e at least 3 independent samples).

If there are more than two dependent samples, we must use the ANOVA with repeated measurements.

ANOVA asks "Is there a difference in the population between the different groups (classified by the independent variable) with respect to the dependent variable".
I.e is there a difference in ages between groups using different statistics packages?

It does not give any information about the direction of the relationship.

Example

Is there a difference in age between users who use different statistic packages?
anovaExample.png

[!INFO] What is the null hypothesis for an ANOVA (one way)?
The null hypothesis is "there are no differences between the means of the individual groups".
The alternative is "there is a difference between at least two of the groups.

ANOVA compares a categorical variable to a continuous variable.

How much of the variation in the mean between the groups is explained by division of the population into the selected groups?
ANOVA2.png
ANOVAVariaceWithinVsBetweenGroups.png

Variance

$$
Sample\ variance = s^2 = \frac{Sum\ of\ Differences\ of\ Squares}{Degrees of freedom}=\frac{\Sigma (x-\bar{x})^2}{n-1}
$$
"Sample variance" here actually means "estimate of the population variance" based on the variance of the sample that we have. Hence, the sum of differences is divided by n-1 and not n. (where n = sample size).


typesOfScleroderma.png

CREST syndrome

The acronym "CREST" refers to the five main features: calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia.
Raynaud's phenomenon can precede the others by a long time. Source

- Beak like nose and microstomia
- telangiectasiaa and dilated nail fold capillary loops. 

sclerodermaComplications.png

Diagnosis

Caused by #autosomal-Recessive defect in ATP7B gene on Chromosome 13 which affects a copper transporting ATPase.
No male / female predominance.